Abstract

Conflicting evidence exists about the effect of angiotensin‐converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) on COVID‐19 clinical outcomes. We aimed to provide a comprehensive/updated evaluation of the effect of ACEIs/ARBs on COVID‐19‐related clinical outcomes, including exploration of interclass differences between ACEIs and ARBs, using a systematic review/meta‐analysis approach conducted in Medline (OVID), Embase, Scopus, Cochrane library, and medRxiv from inception to 22 May 2020. English studies that evaluated the effect of ACEIs/ARBs among patients with COVID‐19 were included. Studies’ quality was appraised using the Newcastle‐Ottawa Scale. Data were analyzed using the random‐effects modeling stratified by exposure (ACEIs/ARBs, ACEIs, and ARBs). Heterogeneiity was assessed using I2 statistic. Several subgroup analyses were conducted to explore the impact of potential confounders. Overall, 27 studies were eligible. The pooled analyses showed nonsignificant associations between ACEIs/ARBs and death (OR:0.97, 95%CI:0.75,1.27), ICU admission (OR:1.09;95%CI:0.65,1.81), death/ICU admission (OR:0.67; 95%CI:0.52,0.86), risk of COVID‐19 infection (OR:1.01; 95%CI:0.93,1.10), severe infection (OR:0.78; 95%CI:0.53,1.15), and hospitalization (OR:1.15; 95%CI:0.81,1.65). However, the subgroup analyses indicated significant association between ACEIs/ARBs and hospitalization among USA studies (OR:1.59; 95%CI:1.03,2.44), peer‐reviewed (OR:1.93, 95%CI:1.38,2.71), good quality and studies which reported adjusted measure of effect (OR:1.30, 95%CI:1.10,1.50). Significant differences were found between ACEIs and ARBs with the latter being significantly associated with lower risk of acquiring COVID‐19 infection (OR:0.24; 95%CI: 0.17,0.34). In conclusion, high‐quality evidence exists for the effect of ACEIs/ARBs on some COVID‐19 clinical outcomes. For the first time, we provided evidence, albeit of low quality, on interclass differences between ACEIs and ARBs for some of the reported clinical outcomes.

Highlights

  • Soon after the report of first clusters of COVID-19 cases in China in December 2019, concerns were raised among clinicians and investigators that angiotensin-convertingenzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) might increase susceptibility to COVID19 infection and the likelihood of severe and fatal COVID-19 illness.[1]

  • These concerns are based on the concept that angiotensin-convertingenzyme 2 (ACE2), an enzyme potentially upregulated by ACEIs/ ARBs use, is the viral entry receptor that COVID-19 uses to enter lung cell,[2] coupled with the observation of high prevalence of hypertension and other cardiovascular comorbidities among COVID-19 patients who have poor outcomes.[3]

  • There appears to be no evidence of association between ACEIs/ARBs use and a wide range of COVID-19-related clinical outcomes

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Summary

Introduction

Soon after the report of first clusters of COVID-19 cases in China in December 2019, concerns were raised among clinicians and investigators that angiotensin-convertingenzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) might increase susceptibility to COVID19 infection and the likelihood of severe and fatal COVID-19 illness.[1]. Endorsement of hydroxychloroquine resulted in drug shortages for other indications, price hikes, increased adverse drug reactions, and deaths from suicides.[12,13] subsequent studies failed to show clinical benefit resulting in the World Health Organisation (WHO) and the National Institute of Health (NIH) in the USA stopping the hydroxychloroquine arm in their studies.[14,15,16] A similar situation has been seen with lopinavir/ritonavir.[15] it is imperative that any considerations regarding management are evidence based

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